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Biomedical subjects

D Smith

Publications and source records attributed to D Smith.

At least 793 records · Page 44Linked to original sources
PubMed1991

Treatment and prophylaxis of Pneumocystis carinii pneumonia in AIDS patients.

Pneumocystis carinii pneumonia (PCP) is seen in people with a defect in cell-mediated immunity. Today the most common cause for this is the Acquired Immunodeficiency Syndrome (AIDS). There have been some remarkable advances recently in the development of new drug regimens to combat this otherwise fatal infection. Although cotrimoxazole (trimethoprim-sulfamethoxazole) is still the drug of first choice it cannot be tolerated by a significant proportion of patients, and therapies such as pentamidine (pentamidine-isethionate) [intravenous or nebulised], dapsone-trimethoprim, eflornithine (DFMO; difluoromethylornithine), trimetrexate, and clindamycin-primaquine are finding therapeutic niches. The major advantage in these other agents is not improved efficacy but different toxicity profiles, enabling therapy to be most appropriately tailored to individual patients' conditions. Although the majority of patients should now survive an attack of PCP, relapses will occur if prophylaxis is not used. There is also the capacity to predict accurately which patients are at risk for this pneumonia and prevent it through the use of chemoprophylaxis. These advances in the treatment and prevention of PCP, together with anti-retroviral therapy, mean that this is an area of AIDS management that has resulted in improved long term survival.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Pathogenesis of corneal epithelial defects: role of plasminogen activator.

Previous studies have suggested that the plasminogen activator (PA)/plasmin system has important roles in the pathogenesis of epithelial defects and stromal ulceration. The current studies were performed to localize PA species and identify them as tissue-type PA (tPA) or urokinase-like PA (uPA) as the two have distinct regulatory properties potentially related to the mechanisms of defect formation and ulceration. To determine the locations and types of PA species, antibodies to tPA or to uPA or the drug amiloride (a drug that inhibits uPA but not tPA) were incorporated into fibrin/fibronectin (Fn) clots overlying frozen sections to block regional fibrinolysis. Normal rabbit eyes showed tPA activity in association with corneal epithelium, corneal endothelium, and ciliary body/iris. After epithelial scrape or alkali burn, corneal tPA activity was detected initially in the defect zone colinear with fibrin/Fn and was symmetrical to resurfacing epithelium. The observation that initial fibrinolysis occurs in the defect zone, known to contain fibrin/Fn, suggests that tPA from blood (limbal vascular endothelium) and/or from corneal epithelium has become bound to (and activated on) the fibrin/Fn. PA activity was also associated with the leading edges of migrating epithelium post-scrape and post-burn and was not inhibited by antibodies to either tPA or uPA but was inhibited by amiloride. After complete closure of the primary defect post-scrape, only tPA appeared to be associated with the epithelium in that all PA activity was inhibited by antibodies to tPA. The observation that leading edge activity post-burn, in correlation with the formation of secondary defects, continues to be inhibitable by amiloride but not by antibodies to tPA suggests that uPA remains abnormally on the leading edge, and that sustained uPA activity in that location results in inappropriate degradation of subepithelial fibrin/Fn to result in a defect. Successful regulation of uPA activity at the leading edge of corneal epithelium post-burn would be expected to be useful therapeutically in the healing of epithelial defects and the prevention of stromal ulceration.

Animals↗
PubMed1991

Mitochondria, oxygen and reperfusion damage.

Reperfusion of the ischaemic or hypoxic heart elicits a number of oxygen dependent processes such as cell lysis and Ca2+ uptake. It is known that the energisation of mitochondria, which requires oxygen, plays a key role in these processes and that the organelle actively sequesters Ca2+ under these circumstances. In this brief review we discuss how oxidants derived from mitochondrial electron transport may perturb mitochondrial calcium handling on reoxygenation of the hypoxic myocardium. In addition we show that the immunosuppressive agent cyclosporin has little or no effect on the oxygen dependent increase in total cell Ca2+ which occurs when hypoxic myocytes are reoxygenated. This result suggests that the Ca2+ dependent mitochondrial pore, which is known to function under conditions of oxidative stress, does not play a major role in the perturbation of Ca2+ homeostasis which occurs on reoxygenation of hypoxic hearts.

Adenosine Triphosphate↗
PubMed1991

Dynamic electromyography in active and limited walking below-knee amputees.

Walking electromyography was performed in 12 below-knee amputees, who were amputated for peripheral vascular insufficiency. All were at least 1 year post-surgery and had no problems with the fit of their prostheses. Seven were community walkers and five were limited household ambulators. The quadriceps and hamstring muscles exhibited electrical activity during 60% and 64.7% of the gait cycle, respectively, in the active walkers, compared with 44.6% and 53.8% in the limited walkers. Quadriceps muscle activity was initiated almost 10% earlier in the active walkers, while hamstring muscle initiation was similar in both groups. The active walkers were able to maintain quadriceps and increase hamstring muscle activity to compensate for their absent ankle motors, while the limited walkers showed decreased activity in both muscle group. The results of this preliminary study suggest that the dysvascular limited walking below-knee amputee does not use the quadriceps and hamstring muscles for propulsion during walking, and does not appear to reap the benefits of knee joint preservation.

Aged↗
PubMed1991

[Direct percutaneous access to the ureter: percutaneous ureterostomy].

Ureteral occlusion with proximal ureteral urinary diversion is usually required in patients with ureteral fistulae secondary to malignant disease. Palliative endourologic management as described with the percutaneous ureterostomy is a viable alternative in treating ureteral fistulae in this patient population.

Colonic Diseases↗
PubMed1991

Carbamazepine-hypersensitivity: assessment of clinical and in vitro chemical cross-reactivity with phenytoin and oxcarbazepine.

1. Seven patients clinically diagnosed as being hypersensitive to carbamazepine and one patient hypersensitive to both carbamazepine and oxcarbazepine have been identified. They have been compared with a control group (hereafter referred to as 'control subjects') comprising five patients on chronic carbamazepine therapy without adverse effects and 12 healthy volunteers who have never been exposed to anticonvulsants. 2. An in vitro cytotoxicity assay employing mononuclear leucocytes as target cells has been used first, to determine the ability of 10 different human livers to bioactivate carbamazepine to a cytotoxic metabolite, and secondly, to compare the cell defences of carbamazepine-hypersensitive patients and control subjects to oxidative drug metabolites generated by a murine microsomal system, using a blinded protocol. 3. With human liver microsomes, the metabolism-dependent cytotoxicity of carbamazepine increased with increasing microsomal protein concentration. At a protein concentration of 2 mg per incubation, the cytotoxicity of carbamazepine with human liver microsomes (n = 10 livers) increased from 7.2 +/- 0.8% (baseline) to 16.4 +/- 2.1% (with NADPH; P = 0.002). 4. In the presence of phenobarbitone-induced mouse microsomes and NADPH, the mean increase in cytotoxicity above the baseline with carbamazepine was significantly greater (P less than 0.001) for the cells from the carbamazepine-hypersensitive patients (7.9 +/- 0.8%) than from control subjects (2.6 +/- 0.3%). 5. In the presence of phenobarbitone-induced mouse microsomes and NADPH, there was no significant difference in cytotoxicity between the cells from carbamazepine hypersensitive patients and from control subjects in the presence of either phenytoin or oxcarbazepine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Acute mountain sickness susceptibility, fitness and hypoxic ventilatory response.

In a party of 17 subjects who travelled together to 4,500 m, hypoxic ventilatory response (HVR) and maximum oxygen consumption (VO2max) were measured before departure. HVR was measured under constant and varying alveolar carbon dioxide tension (PACO2) conditions. VO2max was measured by both standard expired gas collection technique on a treadmill and using the "shuttle run" technique. On arrival at altitude, symptoms of acute mountain sickness (AMS) were scored daily for three days. There were no cases of severe AMS but half of the party had mild to moderate degrees of AMS. There was no correlation between AMS scores and HVR by either method of measurement or with VO2max measured by either method of measurement or with VO2max measured by treadmill or shuttle run.

Acute Disease↗
PubMed1991

Rewarming postoperative patients: lights, blankets, or forced warm air.

This study was designed to determine if the forced warm air system is more effective than warmed cotton blankets or radiant heat lamps for rewarming postoperative patients. PACU admission temperatures were taken on 370 adult patients. The study population of 90 patients with admission temperatures of 35 degrees C (95 degrees F) or less was randomly assigned to one of three intervention groups: (b) warmed cotton blankets, (L) radiant heat lamps, or (A) forced warm air. Oral or axillary temperatures were monitored every 15 minutes and the warming intervention continued until the patient reached the discharge criteria of 36 degrees C (96.8 degrees F). The three groups were comparable for sex, age, admitting temperature, OR time, and OR fluid. The mean rewarming times for patients who shivered were similar for all groups. For those patients who did not shiver, those treated with forced warm air rewarmed significantly faster than patients in the other groups. Nonshivering patients treated with forced warm air were ready for discharge somewhat sooner than those treated with either of the other two interventions.

Body Temperature Regulation↗
PubMed1991

Oxygen radical production by avian leukocytes.

Oxygen radical production by heterophils of red-tailed hawks and chickens, and by neutrophils of calves, was evaluated in a chemiluminescence microassay. Leukocytes were isolated by centrifugation of blood in capillary tubes and then challenged with opsonized zymosan in the presence of luminol. Avian heterophils produced significantly fewer oxygen radicals than did bovine neutrophils.

Analysis of Variance↗
PubMed1991

Intraarterial cisplatin in the management of stage IIB osteosarcoma in the pediatric and adolescent age group.

Sixty patients with extremity osteosarcoma were treated with intraarterial cisplatin. This was followed by surgical resection (amputation or limb salvage) and postoperative adjuvant chemotherapy utilizing two different protocols. Seventy-five percent of patients achieved an initial response. Overall disease-free survival was 58%. The number of patients treated with limb-salvage surgery gradually increased to the extent that 80% of newly-registered patients achieved a response and were subjected to limb salvage. Disease-free survival was 48% in amputation and 68% in limb salvage. The only factors found to have prognostic significance in determining disease-free survival were extent of tumor destruction induced by preoperative chemotherapy and tumor size.

Adolescent↗
PubMed1991

Bromocriptine-associated headache: possible life-threatening sympathomimetic interaction.

We present two cases of severe headache associated with the use of bromocriptine for lactation suppression in otherwise healthy women. In each case, the additional use of a therapeutic sympathomimetic agent resulted in extreme worsening of symptoms with development of hypertension and life-threatening complications (ventricular tachycardia and cardiac dysfunction in one case, seizures and cerebral vasospasm in the other). Sympathomimetics in combination with bromocriptine in patients with a bromocriptine-associated headache during the puerperium may be dangerous.

Adult↗
PubMed1991

DWI Task Forces.

Explore the source record for details and available documents.

Accidents, Traffic↗
PubMed1990

Evidence suggesting negative regulation of the erythropoietin gene by ribonucleoprotein.

The promoter regions of the mouse and human erythropoietin genes have regions of identity within 130 base pairs upstream of the cap site, suggesting a cis-acting regulatory role for the conserved sequences. We have used a double-stranded deoxyoligonucleotide corresponding to the -61 to -45 region relative to the start site of transcription of the mouse gene in DNA mobility shift assays. Nuclear extracts from kidneys of both control and cobalt-stimulated mice contain factors that bind to this oligonucleotide in a specific manner. One factor is a 47-kDa protein, whereas the others may be one or more ribonucleoproteins. Under denaturing conditions, four RNA species which show specific binding to the oligonucleotide were observed, suggesting that recognition of the oligonucleotide by ribonucleoprotein is mediated by the RNA component. In nuclear extracts of kidneys from stimulated animals, the amount of the two largest RNA species that bind to the oligonucleotide was reduced relative to that of control, whereas the other RNA species as well as the 47-kDa protein remained relatively unaffected. These results suggest that the ribonucleoprotein containing the down-regulated RNA species may be a negative transcriptional factor and that activation of the erythropoietin gene by cobalt salts may involve, in part, decreased binding of this factor, thus allowing transcription to proceed.

Animals↗
PubMed1990

Antibodies raised against different portions of A4 protein identify a subset of plaques in Down's syndrome.

Antisera were raised to peptides corresponding to residues 1-10 and 12-28 of the published sequence of A4 protein, a 42/43 amino acid long peptide isolated from the brains of patients with Down's syndrome and Alzheimer's disease. Immunohistochemical studies performed on sections of temporal lobe from 12 cases of Down's syndrome showed that the number of senile plaques in the molecular layer of the dentate gyrus which were identified by antibody to A4(1-10) was only 23% (range 11-53%) of that recognised by antibody to A4(12-28). This observation has important consequences for both the diagnosis and the pathogenesis of Down's syndrome and Alzheimer's disease.

Adult↗
PubMed1990

Biological properties of a CD4 immunoadhesin.

Molecular fusions of CD4, the receptor for human immunodeficiency virus (HIV), with immunoglobulin (termed CD4 immunoadhesins) possess both the gp120-binding and HIV-blocking properties of recombinant soluble CD4, and certain properties of IgG, notably long plasma half-life and Fc receptor binding. Here we show that a CD4 immunoadhesin can mediate antibody-dependent cell-mediated cytotoxicity (ADCC) towards HIV-infected cells, although, unlike natural anti-gp120 antibodies, it does not allow ADCC towards uninfected CD4-expressing cells that have bound soluble gp120 to the CD4 on their surface. In addition, CD4 immunoadhesin, like natural IgG molecules, is efficiently transferred across the placenta of a primate. These observations have implications for the therapeutic application of CD4 immunoadhesins, particularly in the area of perinatal transmission of HIV infection.

Acquired Immunodeficiency Syndrome↗